The human genome contains a large number of hypervariable (HVR) sequences which often occur in short, tandemly repeated DNA segments. The copy number variation of such core sequences reveal genetic variation several orders larger than the classical serologic and biochemical genetic markers. While many such families of HVR loci are described in the human genome, their population genetic properties are relatively less well studied. The objective of this project is to rigorously study the population genetic characteristics of several such loci. Families of HVR loci consisting of di- tri- and tetra-nucleotide simple sequence repeats and chi-like core sequences will be studied for population variation. Blood samples from randomly chosen individuals belonging to several diverse ethnically well-defined human populations of the old and the new world will be studied by Southern blot and PCR techniques. Data gathered will consist of the number, size distribution, and frequencies of alleles at these loci characterized by different repeat unit lengths. Such data will be used to postulate theoretical models to describe the origin and maintenance of HVR polymorphism in human populations. Furthermore, since the populations to be studied in this project are also the ones examined by traditional serologic and biochemical markers, it will be possible to contrast intra- as well as inter-population variation of HVR loci with those at classical markers. Theoretical work of this project will enable us to examine the effect of known selection regime (at the globin gene regions) on HVR polymorphisms adjacent to these gene regions. Development of new statistical methods for studying polymorphisms with multiple alleles will lead to rigorous attempts to examine the generality and reasons underlying the reported departures from Hardy-Weinberg and linkage equilibrium at the HVR loci and to relate the functional attributes of HVR loci with the multi-model allele size distributions at such loci. Understanding of the population genetic characteristics of hypervariable loci is essential for re-affirming the utility of such polymorphisms for human microdifferentiation studies and for utilizing such loci in gene mapping and forensic identification purposes.